Age-related macular degeneration (AMD) is one of the leading causes of legal blindness in developed countries at present, and mainly affects the elderly at the age of 50 years or older. AMD is a disease caused by age-related changes in the macula and is broadly classified into exudative and atrophic forms. Exudative AMD is a disease in which new blood vessels from the choroid grow into the macula in the elderly, and hemorrhage or an exudative lesion occurs beneath the retinal pigment epithelium or retina, and eventually scar tissue is formed. Atrophic AMD is a disease associated with atrophy of the macular region or accumulation of drusen. Further, a precursor lesion that leads to the development of exudative and atrophic AMD is particularly called early AMD in some cases, and this lesion is considered to be one pathological condition of AMD.
A basic pathological condition of AMD (particularly exudative AMD) is choroidal neovascularization, which is considered to be developed through age-related changes in macular retinal pigment epithelial cells, Bruch's membrane and choroidal vessels as the cause. However, much of the pathogenic cause and mechanism of choroidal neovascularization has not been elucidated yet and future development is expected.
On the other hand, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (generic name: Ebselen, hereinafter referred to as “Ebselen”) has an antioxidative effect and is reported to be useful for cerebral arteriosclerosis and chronic cerebral circulatory insufficiency (Non-patent document 1 and Patent document 1). Further, Ebselen is reported to be useful for a keratoconjunctival disorder such as dry eye or superficial punctate keratopathy (Patent document 2).
As a report of study of the pharmacological effect of Ebselen on neovascularization, Non-patent document 2 reports that Ebselen inhibited ischemia-induced neovascularization in hindlimb tissues of mice, and Non-patent document 3 reports that Ebselen inhibited endogenous hydrogen peroxide-induced carotid artery remodeling and neovascularization in p22phox transgenic mice.
However, these reports show the effect of Ebselen on tissues such as hindlimb blood vessels and carotid arteries. That is, these reports (Non-patent documents 2 and 3) only suggest the effect of Ebselen on other than ocular tissues and do not suggest the pharmacological effect of Ebselen on choroidal neovascularization.
Further, Non-patent document 4 reports the pharmacological effect of Ebselen on neovascularization, however, unlike the previously described reports (Non-patent documents 2 and 3), this document reports that Ebselen ameliorated the progression of microangiopathy and partially restored neovascularization. Specifically, in Non-patent document 4, a study was performed using ZDF (diabetic model) rats, and it is reported that in these models, the renal vascular function was inhibited and the capillary density around the renal tubule was decreased, however, by repeated administration of Ebselen, renal neovascularization was restored. That is, Non-patent document 4 reports the results contradictory to the previously described reports (Non-patent documents 2 and 3) with respect to the pharmacological effect on neovascularization although the study was performed using different model animals, and it does not describe or suggest choroidal neovascularization at all.
As described above, choroidal neovascularization has attracted attention as a basic pathological condition of AMD (particularly exudative AMD), however, much of the mechanism thereof has remained unknown. Further, there is no report of study of the pharmacological effect of Ebselen on choroidal neovascularization, particularly, there is no report of study of the prophylactic and improvement effect of Ebselen on AMD.
On the other hand, it is also known that retinal pigment epithelial cell damage caused by oxidative stress or the like is one of the causes of development or progression of AMD, and its contribution to early and atrophic AMD is considered to be large (Non-patent document 5). Accordingly, protection of retinal pigment epithelial cells against cell damage is considered to be effective as one of the methods for prophylaxis or therapy of AMD (particularly early and atrophic AMD). However, there is no report of study of such a protective effect of Ebselen on cell damage.    Patent document 1: JP-A-2001-261555    Patent document 2: WO 2006/123676    Non-patent document 1: Proc. Natl. Acad. Sci. USA, 100(13), 7919-7924 (2003)    Non-patent document 2: Circulation, 111, 2347-2355 (2005)    Non-patent document 3: Circulation, 109, 520-525 (2004)    Non-patent document 4: Kidney International, 66, 2337-2347 (2004)    Non-patent document 5: Progress in Retinal and Eye Research 19 (2), 205-221, 2000